1. Field of the Invention
The present invention relates to a method for controlling undesirable flow of charged species across, or between, regions of a fluid network such as a separation network. Such systems typically comprise multiple separation channels connected by a common manifold and in those systems where separation is driven by an electrical gradient (electrokinetic pumping), a means for uncoupling species transport between channels is desirable.
Integrated microfluidic networks used for analytical microseparations generally rely on electrokinetic phenomena for control of material transport through the channels. A recurring network topology consists of a distribution manifold connected to many parallel channels. This arrangement, shown schematically in FIGS. 1A and 1B for the case of two channels, enables a common buffer solution or sample to be distributed to all channels, but then allows individual channels to perform different functions.
FIGS. 1A and 1B shows a top view of two states of a microfluidic network 1 of channels fabricated using micromachining techniques. The channel network shown contains two separation channels 2 and 3, manifold 4 and manifold branches 5L and 5R several supply or waste reservoirs 6-12 disposed at terminal ends of channels 2 and 3 and manifold branches 5L and 5R. Programmed electrical voltages may be imposed on each reservoir (or the reservoirs may be floated) using an electrode or electrodes (not shown) in order to induce ionic flow. FIG. 1A shows the state of the network in which a solute sample (e.g., some set of dissolved species) is distributed from negatively charged sample solution reservoir 6 through manifold 4 and “injected” across each of vertical separation channels 2 and 3, and then flows into positively-charged waste reservoirs 9 and 10 while, in this example, the potential of the remaining four reservoirs is floated. The sample (not shown) is carried along by a combination of electrophoresis and electro-osmosis caused by the imposed voltage gradients. While the sample is not shown, the progression of the sample, assumed to comprise species having negative electrokinetic (EK) mobility, is indicated by block arrows 13 and 14 along the left and right arms of manifold 4. Species having a positive EK mobility remain in reservoir 6.
In FIG. 1B, the electrical potentials of sample reservoirs 6 and waste reservoirs 9 and 10 are allowed to float, and voltage gradients are applied along each of channels 2 and 3. (Here, different polarities of voltage gradients are shown to emphasize the fact that the separations in channels 2 and 3 may be different from one another.) Block arrows 15 and 16 now show the desired direction of transport of the sample species “of interest” down the length of the separation channels 2 and 3 respectively. For example, if there were no electro-osmotic flow in the separation channels, positively charged species that have a negative electrokinetic mobility would separate in channel 3, and negatively charged species in channel 2, while oppositely charged species would move to respective waste reservoirs 7 and 8 at the top of channels 2 and 3, and neutral species would remain stationary.
However, it is apparent is that the arrangement illustrated in FIG. 1B can produce unwanted electrical “cross-talk” between the two separation channels, creating a current indicated by line arrows 17. Therefore, in addition to the desired transport of species through a particular channel, this “cross-talk” can transport ionic species between the coupled channels through the manifold.
2. Prior Art
A solution to the problem of this spurious ionic flow is the subject of the present invention. The simplest conceptual scheme would be a mechanical valve, where a solid element is slid across, or is rotated into and out of, the channel, thereby greatly reducing the cross sectional area of the separation channel. Although miniature valves are common, all examples known to the Applicants have dead volumes that are one or more orders of magnitude too large for use in the proposed microfluidic network. Numerous problems with tolerances, stiction, and limitations of micromachining materials and methods make the use of a mechanical valve extremely challenging for microfabricated microfluidic networks.
An alternate approach to providing a reversible barrier would be to generate a gas bubble along the flow path (channel) since, clearly, a channel whose cross section contains such a bubble has a lower ionic conductance than an unobstructed channel containing only the conducting solvent medium. However, given the dangers of gas bubbles becoming entrained in the solution and/or migrating uncontrollably, localization and reversibly of bubble formation is absolutely essential. That is, the need for an independently controllable means for both generating and eliminating localized gas bubbles is critical to the proper operation of this invention. In the specific case of an electrokinetic switch (“EK switch”) relying on a gas bubble, if the bubble escapes from confinement in the switch region and blocks conductance through a channel, there may be no means to reestablish ionic conduction and fluid transport through that channel.
Numerous references to the use of in situ generated bubbles exist in the prior art. In particular, various U.S. patents contained in class 347, and particularly U.S. Pat. Ser. No. 6,062,681 to Field, et al., describe the use of bubbles as elements to control ink flow in print heads of ink-jet printer cartridges. Furthermore, Field, et al, refer to a publication by Thomas K. Jun and Chang-Jin Kim entitled “Microscale Pumping with Traversing Bubbles In Microchannels” (SOLID-STATE SENSOR AND ACTUATOR WORKSHOP, HILTON HEAD, SOUTH CAROLINA, 144-147, Jun., 2-6, 1996) that suggest that a stationary vapor bubble formed by boiling a liquid flowing through a channel could serve as an obstruction against flow in the channel and therefore function as a valve. However, such a valve is impractical in a typical liquid that includes dissolved gas because flow of liquid cannot easily be restored.
Field, et al. also refer to the dissertation of Liwei Lin, entitled “Selective Encapsulations of [Micro Electro-Mechanical Systems]: Micro-Channels, Needles, Resonators and Electro-mechanical Filters”, University of California at Berkeley, 1993, also describes forming and moving bubbles within microchannels. The bubbles were formed by using micro-heaters to heat the liquid to a temperature close to its critical temperature. This reference also describes the effect of the shape of the flow channel on the preferred direction of movement of the bubble
Finally, U.S. Pat. No. 5,699,462 of Fouquet et al., describes using gas or vapor bubbles as switching elements for controlling the passage of optical communication signals through waveguides. This patent also describes forming the bubbles by using micro-heaters to heat the liquid. Bubble formation is enhanced by use of a gas dissolved in the fluid. The bubble is moved by creating a second bubble to force the first from its location.
The use of a bubble as a control element in a fluid channel, therefore, has been described. However, to limit the position of the bubble to a specific location within a fluid network, has not been described. That is, the prior art provides no teaching for how a gas bubble could be reversibly created and extinguished nor how its position could be maintained to provide process localization. Furthermore, the means taught by these references for creating and elimination bubbles is limited to the use of a heater element.
Other methods for eliminating gas bubbles such as by venting, dissolving, or reacting or condensing the gas, or by applying high pressure to reduce the size of the bubble are possible. Venting bubbles controllably, in the sorts of structures needed for microfluidic networks, however, requires the ability to pressure-flush the bubble into a micro-machined purgeable bubble trap. Although such an approach may be possible, the complexities of such a micro-machined design are considerable. Rapid injection or electrolytic generation of a highly soluble gas could be used to create a bubble that has a finite lifetime. However, this creates a danger of outgassing at some other point in the network, and highly soluble gasses (e.g., ammonia) may greatly disrupt the pH or other properties of the solution. Reacting (chemically scrubbing) the gas bubble appears to raise many of the same complexities.